The present embodiments relate to an ion concentration sensor, and, more particularly, an ion concentration sensor based upon an ion sensitive transistor.
Ion concentration measurements, particularly pH (potential of Hydrogen) measurements, are performed routinely in the chemical, biochemical, biomedical, and other fields. In the biomedical field, for example, a pH sensor may be used during neurosurgery to perform brain monitoring via CSF, blood pH measurement, and biotelemetry. A variety of ion concentration sensors are available for performing these measurements. One class of ion concentration sensors is based on ion sensitive transistors, such as the ion sensitive field effect transistor (ISFET). The ion sensitivity that is observed when the transistor is exposed to an electrolyte makes the ISFET a highly useful tool for pH sensors used in many fields, such as agriculture, environmental studies, and the food industry.
The ISFET is based on the structure of Metal-Oxide-Semiconductor (MOSFET). In an ISFET, the metal gate contact of the MOSFET is eliminated, exposing the gate insulator. The gate insulator can thus contact an electrolyte solution, when the ISFET is immersed in the solution. The ISFET sensing principle is based on charge absorption at the ion-solid interface between the sensing layer, which contains hydroxyl groups, and the electrolyte, from which hydroxyls may accept or donate protons. In this process, a double-layer capacitance is created with a potential drop which influences the threshold voltage of the transistor, so that the threshold drop corresponds to the ion concentration.
FIG. 1 shows a typical cross-section of an ISFET. Like a MOSFET, ISFET 100 contains reference electrode 110 which provides contact to the transistor gate, and two diffusion connections 120.1 and 120.2. ISFET 100 also has ion sensitive layer 130, which can contact the test solution.
The ISFET has an insulating layer applied on top of the gate structure, so the gate voltage is applied to a reference electrode. The ISFET threshold voltage is dependent on the interfaces between the reference electrode and the solution, and between the solution and the oxide on the gate. The flat-band voltage is therefore:
                              V          FB                =                              E            ref                    -                      Ψ            0                    +                      χ            sol                    -                                    Φ              Si                        q                    -                                                    Q                ss                            +                              Q                ox                                                    C              ox                                                          (        1        )            where ΦSi is the silicon work-function, Qss is the surface state density at the silicon surface, and Qox is the fixed oxide charge, Eref is a constant related to the reference electrode potential, and χsol is the constant surface dipole potential of the solution. The surface potential Ψ0 is created by chemical reactions between the hydroxyl groups with the surfaces of the oxide and the aqueous solution. During the chemical reactions, the hydroxyl sites bind or release hydrogen ions, creating a charge on the oxide surface that is opposite to the ion charge in the solution. In this way a double layer structure is created with capacitance Cdl and a variable potential drop Ψ0. Potential drop Ψ0 operates as a serial voltage source to the gate electrode, and is linearly dependent on the hydrogen ion concentration in the solution (pH).
FIG. 2 shows the ISFET equivalent electrical circuit, containing FET 210, double layer capacitance Cdl 220, and current source 230. Current source 230 represents the charge resulting from the potential drop To on the double layer capacitor. The ISFET's sensitivity is defined by the linear dependence Ψ0/pH, and for high-performance sensors can reach up to 58 mV/pH.
Currently, ISFET-based ion concentration sensors require additional readout circuitry, in order to convert the ISFET electrical response to values corresponding to the ion concentration in the solution. The main reason for the use of a readout circuit is that pH fluctuations influence the threshold voltage, which is an internal FET parameter, and do not manifest themselves as a voltage signal at the output but rather as fluctuations of the transconductance. Transconductance is a passive parameter, so that deriving a voltage or current signal from the transconductance fluctuations requires attaching the sensor to conditioning and transmitting circuitry.
In order to obtain a measurement signal, the ISFET is associated with an analog interface circuit. When a constant drain-source voltage, Vds, is applied, the ISFET itself converts the input voltage, Ψ0, into a corresponding channel resistance, which manifests itself as a certain drain current, ID. The ISFET response is described by P. Bergveld and A. Sibbald in “Analytical and Biomedical Applications of Ion-Selective Field Effect Transistors”, Comprehensive Analytical Chemistry, vol. 12, 1988, which is hereby incorporated by reference. The readout circuit commonly couples the ISFET to devices such as operational amplifiers, current sources, and MOSFETs, which are combined in various feedback configurations. The readout circuit maintains the drain current and/or the drain-source voltage of the ISFET at a constant level.
Two examples of prior art ISFET readout interfaces are presented below. The configurations differ in structure, bias conditions, and the way the feedback signal is applied. These factors impact the complexity, performance (sensitivity, noise limits, etc.), and second-order effects (such as the body effect) of the readout circuit.
A first example of a prior-art readout circuit is the source-drain follower configuration shown in FIG. 3. The readout circuit is configured as an instrumental amplifier, and is realized with operational amplifiers A1, A2, and A3, with internal amplification equal to:
                              (                                                    r                ds                            +                              2                ⁢                                  R                  3                                                                    r              ds                                )                ⁢                                            R              5                                      R              4                                .                                    (        2        )            
The ISFET operates in the linear region, with a constant drain-source voltage Vds=I1·R1 for a constant ID. The ISFET replaces a resistor within the instrumental amplifier configuration, so that the amplification factor varies in accordance with the properties of the ISFET. The change of the threshold voltage, Vth, is amplified at the R6 output by:
                              Δ          ⁢                                          ⁢                      V            out                          =                  Δ          ⁢                                          ⁢                                    V              th                        ·                          (                                                R                  6                                                  R                  2                                            )                                                          (        3        )            
The ISFET source and drain connections are symmetrical, and have low resistance due to the internal feedback of amplifiers A1 and A2. The source-follower configuration is thus attractive for discrete implementations containing long wires.
The source-follower configuration is widely used in discrete implementations, but requires a large amount of hardware (four operational amplifiers and nine resistors), which makes it inapplicable for monolithic Microsystems with limited chip area. Note also that in monolithic implementations in CMOS technology the source-follower circuit is affected by the body effect of the n-channel ISFET. The source-drain follower readout circuit is therefore not suitable for monolithic Microsystems which are based on n-channel ISFETs, due to their low drift properties. This problem is not limited to the source-follower readout circuit, but occurs in many other configurations.
A second example of a readout circuit is the constant current driver shown in FIG. 4a. The constant current driver circuit uses the same principle as the source-drain follower, and can be integrated into discrete circuits or monolithic circuits with p-type ISFETs. The constant current driver configuration is discussed in P. Bergveld “Development of an Ion-Sensitive Solid-State Device for Neurophysiological Measurements”, IEEE Trans. Biomedical Engineering, MBE-17, p. 70, 1970, and by S. Casans, D. Ramirez and A. E. Navarro in “Circuit Provides Constant Current for ISFETs/MEMFETs”, EDN Access, Design Ideas, 2000, which are both hereby incorporated by reference. Current source I1 produces a voltage drop across resistor R1. The voltage follower reflects this voltage at the drain-source terminals of the ISFET as:Vds=I1·R1.  (4)The drain current is kept constant via I2. The ISFET works in linear region. Vout, with:
                              V          out                =                              -                                          V                th                            ⁡                              (                ISFET                )                                              -                                    I              2                                      β              ·                              I                1                            ·                              R                1                                              -                                                    I                1                            ·                              R                1                                      2                                              (        5        )            
Although, the structure of constant current driver readout circuit is somewhat simplified, it still suffers from the body effect in n-type ISFET, and thus is unsuitable for application in CMOS microsystems.
Another example of a readout circuit is the ISFET/MOSFET differential pair configuration shown in FIG. 4b. The readout circuit is based on the integration of an ISFET and a MOSFET in a differential amplifier circuit, with voltage feedback of the output signal to the MOSFET gate, a concept known as indirect feedback. The ISFET drain current is thus kept constant, to compensate for the solid-state temperature sensitivity without using a differential ISFET configuration.
The amplification of the ISFET/MOSFET Differential Pair circuit is:
                                          ∂                          V              out                                            ∂                          Ψ              0                                      =                  A                      A            +            1                                              (        6        )            Thermally induced changes in the ISFET and MOSFET drain currents are rejected by the differential input stage as a common mode signal. However, the ISFET body effect makes the ISFET/MOSFET differential pair configuration problematic for implementation in CMOS Microsystems.
An additional example of a readout circuit is the source follower configuration for discrete systems shown in FIG. 4c. This configuration is described by C. G. Jakobson and Y. Nemirovsky, in “1/f Noise in Ion Sensitive Field Effect Transistors from Subthreshold to Saturation”, in IEEE Trans. on Electron Devices, vol. 46, pp. 259-261, 1999, which is hereby incorporated by reference. The readout circuit implements the principle of source follower for discrete applications, while eliminating the voltage drop on connecting wires by using operational amplifiers as shown in FIG. 4c. 
Readout circuit operation is based on the following relationships:ID=VREF/(R1+R2)  (7)VOUT=VDS=VGS(pH)  (8)The discrete system source follower allows simultaneous measurement of n-channel and p-channel ISFET sensors, while maintaining a constant drain current. Changes in VT due to a changing pH manifest themselves in changes in ID, causing an increase in VOUT which returns the current to initial value.
The loop transmission of the circuit is:LT=AV·gm·R  (9)so that the stability of the circuit can be controlled by the value of R. The capacitor, C, is added for zero-pole compensation.
Body effect considerations affect the use of this configuration in CMOS monolithic microsystems. When the feedback signal returns to the source, the signal causes a |VBS|>0 in the n-channel ISFET, resulting in an additional increase in VT that is not due to the pH value. The VT increase is applied once again to the amplifier stage, and results in restrained oscillations leading to a final incorrect value which is larger than the desired result.
Other readout circuits are found in the prior art, but all require adding additional components to the ISFET in order to obtain a voltage which accurately reflects the ion concentration of the sensed environment. Although the existing readout techniques are widely used in discrete system applications, only a few interfaces are suitable for integration in a microsystem in CMOS technology due to body effect concerns. N-channel ISFETs are generally used in CMOS-based integrations, due to low drift properties, with the p-type substrate globally and constantly grounded. Grounding the p-type substrate limits the possibilities of source biasing in ISFET. None of the prior-art techniques supplies a full assembly of high-performance features, such as constant values of Id and/or Vds, body effect elimination, low temperature sensitivity, and design simplicity.
The disadvantages of current transistor-based ion concentration sensors with readout circuits are numerous, and include large area, higher power consumption, more bandwidth and stability limitations, and increased design complexity. Solving these problems could have potential uses for numerous fields, including biomedical applications, such as array-type monitoring in biotelemetry and miniaturized clinical applications.
There is thus a widely recognized need for, and it would be highly advantageous to have, an ion concentration sensor devoid of the above limitations.